The MIT Program of 'Molecular Physiology of the Heart and its Vasculature' will investigate the molecular biology of the heart and appropriately related tissues, and the abnormalities that lead to cardiovascular disorders. It's main goals are to identify biochemical, cell biologic, and genetic determinants that underlie normal cardiac vascular development and cardiovascular function and that, when altered, predispose or cause individuals to develop cardiovascular diseases. The work will focus primarily on murine models of physiology and pathology and the use of molecular biology and genetics and expand our knowledge of the function and malfunction of the cardiovascular system. This work is expected to contribute significantly to the elucidation of the basic molecular physiologic mechanisms required for future genetics-based, targeted advances in the diagnosis, treatment and prevention of cardiovascular disease. The Program links together and will foster extensive interactions among senior faculty members of the MIT Department of Biology. These investigators employ a variety of molecular biologic approaches to study the structure and function of the cardiovascular system. They have been uncovering unsuspected biochemical pathway unsuspected biochemical pathways of gene expression with somatic genetic techniques; elucidating the biologic effects of specific genes at the whole organism level and developing novel disease model systems by employing transgenic/chimeric/knockout mouse models; and delineating the molecular basis of human diseases with novel gene mapping techniques. The nature of the various projects involves extensive collaboration among Program participants, who will contribute a wide variety of molecular, cellular, genetic, genomics and physiologic approaches to the resolution of common problems. The overall Program will be strengthened by shared facilities for transgenic mice, cell culture, and administration. This Program Project proposal is an outgrowth of the highly successful 12 year MIT Program of Excellence in Molecular Biology (POEMB) sponsored by the NHLBI. Based on the POEMB experience, we expect that the proposed network of interactions will accelerate research accomplishments in the individual laboratories and significantly contribute to our understanding of cardiovascular physiology and pathophysiology.